Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways

Abstract

Salvianolic acid B (SalB), a natural polyphenolic compound extracted from the herb of Salvia miltiorrhiza, possesses antioxidant and neuroprotective properties and has been shown to be beneficial for diseases that affect vasculature and cognitive function. Here we investigated the protective effects of SalB against subarachnoid hemorrhage (SAH)-induced oxidative damage, and the involvement of underlying molecular mechanisms. In a rat model of SAH, SalB inhibited SAH-induced oxidative damage. The reduction in oxidative damage was associated with suppressed reactive oxygen species generation; decreased lipid peroxidation; and increased glutathione peroxidase, glutathione, and superoxide dismutase activities. Concomitant with the suppressed oxidative stress, SalB significantly reduced neurologic impairment, brain edema, and neural cell apoptosis after SAH. Moreover, SalB dramatically induced nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased expression of heme oxygenase-1 and NADPH: quinine oxidoreductase-1. In a mouse model of SAH, Nrf2 knockout significantly reversed the antioxidant effects of SalB against SAH. Additionally, SalB activated sirtuin 1 (SIRT1) expression, whereas SIRT1-specific inhibitor sirtinol pretreatment significantly suppressed SalB-induced SIRT1 activation and Nrf2 expression. Sirtinol pretreatment also reversed the antioxidant and neuroprotective effects of SalB. In primary cultured cortical neurons, SalB suppressed oxidative damage, alleviated neuronal degeneration, and improved cell viability. These beneficial effects were associated with activation of the SIRT1 and Nrf2 signaling pathway and were reversed by sirtinol treatment. Taken together, these in vivo and in vitro findings suggest that SalB provides protection against SAH-triggered oxidative damage by upregulating the Nrf2 antioxidant signaling pathway, which may be modulated by SIRT1 activation.

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

“…Salviae Miltiorrhizae has many pharmacological activities, such as anti-oxidation, suppressing platelet adhesion and aggregation, improving microcirculation, improving hemorheology, and regulating blood lipids [16][17][18]. The main bioactive ingredients of Salviae Miltiorrhizae injection include several water-soluble bioactive compounds (Danshensu, salvianolic acids, protocatechuic aldehyde, rosmarinic acid, and caffeic acid) [16,[19][20][21][22][23]. Salviae Miltiorrhizae injection also contains trace amount of lipophilic compounds, such as tanshinone II A and cryptotanshinone.…”

“…Salviae Miltiorrhizae injection also contains trace amount of lipophilic compounds, such as tanshinone II A and cryptotanshinone. The cardiovascular actions of Danshensu, and salvianolic acids have been intensively investigated in the past decade, which supports the clinical utility of these compounds against platelet aggregation and thrombus formation, promoting fibrin degradation, protecting against myocardial ischemia, and improving the microcirculation [16,[19][20][21][22][23]. Protocatechuic aldehyde is another hydrophilic component of DHI.…”

“…Protocatechuic aldehyde has many pharmacological effects, such as anti-inflammatory, anti-oxidation, anti-platelet aggregation, regulation of energy metabolism, inhibition of proliferation and apoptosis. Therefore, protocatechuic aldehyde is effective in improving angina pectoris, inhibiting myocardial ischemia-reperfusion (I/R) injury, and cardiomyocyte apoptosis associated with cardiovascular disease [16,[19][20][21][22][23]. Most of the salvianolic acids is composed of Danshensu combined with other organic acid compounds.…”

“…salvianolic acid-A and salvianolic acid-B have been used as important standard indicators for the qualitative and quantitative investigation of bioactive constituents of Salvia Miltiorrhizae. Although salvianolic acids have several types, they have shared pharmacological effects due to their polyphenolic structure: anti-oxidation, scavenging free radicals, suppressing platelet aggregation, protecting cerebral ischemic injury, improving memory dysfunction, and endothelial protection [16,[19][20][21][22][23]. Flos Carthami injection is a traditional Chinese medicine prepared by extracting single-flavored drug-safflower.…”

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

“…The mice were assessed using mNSS test on days 1 and 3 after TBI according to previous studies [34].…”